Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors.
Insulin-like growth factors (Igfs) are key regulators of key biological processes such as embryonic development, growth, and tissue repair and regeneration. The role of Igf in myogenesis is well documented and, in zebrafish, promotes fin and heart regeneration. However, the mechanism of action of Ig...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5802911?pdf=render |
| _version_ | 1818026110958436352 |
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| author | Alfonso Saera-Vila Ke'ale W Louie Cuilee Sha Ryan M Kelly Phillip E Kish Alon Kahana |
| author_facet | Alfonso Saera-Vila Ke'ale W Louie Cuilee Sha Ryan M Kelly Phillip E Kish Alon Kahana |
| author_sort | Alfonso Saera-Vila |
| collection | DOAJ |
| description | Insulin-like growth factors (Igfs) are key regulators of key biological processes such as embryonic development, growth, and tissue repair and regeneration. The role of Igf in myogenesis is well documented and, in zebrafish, promotes fin and heart regeneration. However, the mechanism of action of Igf in muscle repair and regeneration is not well understood. Using adult zebrafish extraocular muscle (EOM) regeneration as an experimental model, we show that Igf1 receptor blockage using either chemical inhibitors (BMS754807 and NVP-AEW541) or translation-blocking morpholino oligonucleotides (MOs) reduced EOM regeneration. Zebrafish EOMs regeneration depends on myocyte dedifferentiation, which is driven by early epigenetic reprogramming and requires autophagy activation and cell cycle reentry. Inhibition of Igf signaling had no effect on either autophagy activation or cell proliferation, indicating that Igf signaling was not involved in the early reprogramming steps of regeneration. Instead, blocking Igf signaling produced hypercellularity of regenerating EOMs and diminished myosin expression, resulting in lack of mature differentiated muscle fibers even many days after injury, indicating that Igf was involved in late re-differentiation steps. Although it is considered the main mediator of myogenic Igf actions, Akt activation decreased in regenerating EOMs, suggesting that alternative signaling pathways mediate Igf activity in muscle regeneration. In conclusion, Igf signaling is critical for re-differentiation of reprogrammed myoblasts during late steps of zebrafish EOM regeneration, suggesting a regulatory mechanism for determining regenerated muscle size and timing of differentiation, and a potential target for regenerative therapy. |
| first_indexed | 2024-12-10T04:26:48Z |
| format | Article |
| id | doaj.art-eaff9418a1b94322b6bbbb0dff0c579f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T04:26:48Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-eaff9418a1b94322b6bbbb0dff0c579f2022-12-22T02:02:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01132e019221410.1371/journal.pone.0192214Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors.Alfonso Saera-VilaKe'ale W LouieCuilee ShaRyan M KellyPhillip E KishAlon KahanaInsulin-like growth factors (Igfs) are key regulators of key biological processes such as embryonic development, growth, and tissue repair and regeneration. The role of Igf in myogenesis is well documented and, in zebrafish, promotes fin and heart regeneration. However, the mechanism of action of Igf in muscle repair and regeneration is not well understood. Using adult zebrafish extraocular muscle (EOM) regeneration as an experimental model, we show that Igf1 receptor blockage using either chemical inhibitors (BMS754807 and NVP-AEW541) or translation-blocking morpholino oligonucleotides (MOs) reduced EOM regeneration. Zebrafish EOMs regeneration depends on myocyte dedifferentiation, which is driven by early epigenetic reprogramming and requires autophagy activation and cell cycle reentry. Inhibition of Igf signaling had no effect on either autophagy activation or cell proliferation, indicating that Igf signaling was not involved in the early reprogramming steps of regeneration. Instead, blocking Igf signaling produced hypercellularity of regenerating EOMs and diminished myosin expression, resulting in lack of mature differentiated muscle fibers even many days after injury, indicating that Igf was involved in late re-differentiation steps. Although it is considered the main mediator of myogenic Igf actions, Akt activation decreased in regenerating EOMs, suggesting that alternative signaling pathways mediate Igf activity in muscle regeneration. In conclusion, Igf signaling is critical for re-differentiation of reprogrammed myoblasts during late steps of zebrafish EOM regeneration, suggesting a regulatory mechanism for determining regenerated muscle size and timing of differentiation, and a potential target for regenerative therapy.http://europepmc.org/articles/PMC5802911?pdf=render |
| spellingShingle | Alfonso Saera-Vila Ke'ale W Louie Cuilee Sha Ryan M Kelly Phillip E Kish Alon Kahana Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors. PLoS ONE |
| title | Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors. |
| title_full | Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors. |
| title_fullStr | Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors. |
| title_full_unstemmed | Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors. |
| title_short | Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors. |
| title_sort | extraocular muscle regeneration in zebrafish requires late signals from insulin like growth factors |
| url | http://europepmc.org/articles/PMC5802911?pdf=render |
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